BACKGROUND/AIMS: Microsatellite instability (MSI) is a genetic alteration observed frequently in gastric carcinoma (GC). To assess the role of microsatellite instability (MSI) in gastric cancer (GC), we investigated the incidence of MSI, especially widespread MSI (MSI-H). METHODS: Endoscopic biopsy specimens from 59 gastric adenocarcinomas were analyzed for MSI at 13 loci. Paraffin-embedded GC samples from the same 59 GC were analyzed for p53 protein overexpression using immunohistochemical staining. RESULTS: MSI was detected in 33/59 (56%). MSI-H in which over than 40% of investigated loci had MSI, was observed in 7 cases (12%) and low MSI (MSI-L), in which less than 40% of the loci had MSI, was observed in 26 cases (44%). All MSI-H found in 7 cases (12%) were located in distal stomach. There was no difference in the incidences of MSI and MSI-H according to the histology of Lauren's classification, TNM stage, presence of metastasis to lymph node and family history of GC. Overexpression of p53 protein was detected in 43/59 (73%) GC, but MSI-H was not related to the p53 overexpression. MSI in interferon-alphaR was observed more frequently in GC with family history than GC without family history (55% vs 3%)(p=0.0002). CONCLUSIONS: MSI and p53 mutation are involved frequently in oncogenesis of GC. MSI-H is frequently observed in distal GC, but is not related with tumor progression and family history of GC.